The renal threshold for bicarbonate has been found to be low in the newborn when compared to the older child and the adult. This results in a decreased buffer base which places the infant at a disadvantage when challenged by a hydrogen ion load. The intrinsic capacity of the tubular membrane to reabsorb bicarbonate does not seem to account for the low threshold since the TM HCO3 is similar in infants and adults and the threshold of the immature animal will rise when alkalosis is produced in the absence of volume expansion. It would appear therefore that the low renal threshold of bicarbonate observed in infants can be due either to an inability of the renal tubule to maintain a steady state bicarbonate gradient between the tubular fluid and the peritubular blood similar to that observed in the adult or to extrinsic factors, such as the state of the extracellular volume and PCO2. The experiments described in this application will use the technique of the isolated perfused tubule which is particularly suited to investigations in which various factors need to be strictly controlled. Using recently developed methods for measurement of pH, titratable acid and bicarbonate, the experiments will seek information regarding: a) net bicarbonate reabsorption, b) tubule permeability to CO2 and bicarbonate, 3) hydrogen ion secretion. The measurement will be peformed on proximal convoluted tubules obtained from rabbits varying in age between birth and 8 weeks of age. The results obtained should permit us to determine whether the low threshold for bicarbonate is a consequence of a low secretory capacity for hydrogen ions, a relative impermeability of the tubular epithelium to CO2, or a larger back-leak of bicarbonate. Since the influence of the extracellular volume cannot play a role in these experiments, its contribution can also be implied.